Evidence map›Paper›PMID 26529632›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2016

Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia.

Michael P Whyte, Cheryl Rockman-Greenberg, Keiichi Ozono, Richard Riese, Scott Moseley, Agustin Melian, David D Thompson, Nicholas Bishop, Christine Hofmann

Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 1 pooled it
17.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed, 1 synthesis or guideline pooled it, 263 citations in OpenAlex.

  1. Hypophosphatasia: Canadian update on diagnosis and management.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019
    Guideline
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Review
  7. Perinatal hypophosphatasia refractory to asfotase alfa with neutralizing antibodies that affected bone mineralization: a case report.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026
    Article
  8. Review
  9. Article
  10. Biochemical phenotype of hypophosphatasia in asymptomatic individuals carrying ALPL variants.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Article
  11. Article
  12. Review
  13. Revisiting the Genetics of Hypophosphatasia.Journal of inherited metabolic disease · 2025
    Review
  14. Review
  15. Hypophosphatasia: A case report.World journal of clinical cases · 2025
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Effects of enzyme replacement therapy in sibling cases of hypophosphatasia of varying severities.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025
    Article

64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 5 countries.

Michael P WhyteShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Cheryl Rockman-GreenbergShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Keiichi OzonoShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Richard RieseShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Scott MoseleyShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Agustin MelianShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
David D ThompsonShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Nicholas BishopShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Christine HofmannShriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.
Alexion Pharmaceuticals (United States) · USChildren's Hospital Research Institute of Manitoba · CAOsaka University · JPSheffield Children's Hospital · GBUniversity of Würzburg · DEWashington University in St. Louis · US

Funding

Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
NCATS NIH HHS UL1 TR000004
6 · The paper itself

Abstract

contextHypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50-100% mortality, typically from respiratory complications.

objectivesOur objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. DESIGN/

settingData from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. PATIENTS: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics.

interventionsTreated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly.

main outcome measuresSurvival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study.

resultsAsfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health.

conclusionsAsfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP.

Indexed as

Age FactorsAlkaline PhosphataseBone DensityChild, PreschoolEnzyme Replacement TherapyFemaleHumansHypophosphatasiaImmunoglobulin GInfantInfant, NewbornInjections, SubcutaneousKaplan-Meier EstimateMaleRecombinant Fusion ProteinsRespiration, ArtificialAlkaline Phosphataseasfotase alfaImmunoglobulin GRecombinant Fusion Proteins

Identifiers

PMID26529632
PMCPMC4701846
OpenAlexW2150512825

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.